COPD and the gut-lung axis: the therapeutic potential of fibre.

Current management strategies for chronic obstructive pulmonary disease (COPD) incorporate a step-wise, multidisciplinary approach to effectively manage patient symptoms and prevent disease progression. However, there has been limited advancement in therapies to address the underlying cause of COPD pathogenesis. Recent research has established the link between the lungs and the gut-the gut-lung axis -and the gut microbiome is a major component.

The potential of siRNA based drug delivery in respiratory disorders: Recent advances and progress.

Lung diseases are the leading cause of mortality worldwide. The currently available therapies are not sufficient, leading to the urgent need for new therapies with sustained anti-inflammatory effects. Small/short or silencing interfering RNA (siRNA) has potential therapeutic implications through post-transcriptional downregulation of the target gene expression.

Therapeutic potential of Artemisia vulgaris: An insight into underlying immunological mechanisms.

Artemisia vulgaris is a traditional Chinese herb believed to have a wide range of healing properties; it is traditionally used to treat numerous health ailments. The plant is commonly called mugwort or riverside wormwood. The plant is edible, and in addition to its medicinal properties, it is also used as a culinary herb in Asian cooking in the form of a vegetable or in soup.

Hypoxia-inducible factor and bacterial infections in chronic obstructive pulmonary disease.

COPD is a seriously disabling respiratory condition that inexorably progresses to disability and mortality. It affects approximately 10% of the population globally with a greater prevalence at advanced ages. Airway bacterial infections complicate the disease course in most COPD patients, leading to increased symptoms, more rapid decline in lung function, acute exacerbations and reduced quality of life.

Cellular mechanisms underlying steroid-resistant asthma.

Severe steroid-resistant asthma is clinically important, as patients with this form of the disease do not respond to mainstay corticosteroid therapies. The heterogeneity of this form of asthma and poor understanding of the pathological mechanisms involved hinder the identification of therapeutic targets and the development of more effective therapies. A major limiting factor in the understanding of severe steroid-resistant asthma is the existence of multiple endotypes represented by different immunological and inflammatory phenotypes, particularly in adults.

Assessment of evidence for or against contributions of Chlamydia pneumoniae infections to Alzheimer's disease etiology.

Alzheimer's disease, the most common form of dementia, was first formally described in 1907 yet its etiology has remained elusive. Recent proposals that Aβ peptide may be part of the brain immune response have revived longstanding contention about the possibility of causal relationships between brain pathogens and Alzheimer's disease. Research has focused on infectious pathogens that may colonize the brain such as herpes simplex type I.

Identification and Optimization of Mechanism-Based Fluoroallylamine Inhibitors of Lysyl Oxidase-like 2/3.

Lysyl oxidase-like 2 (LOXL2) is a secreted enzyme that catalyzes the formation of cross-links in extracellular matrix proteins, namely, collagen and elastin, and is indicated in fibrotic diseases. Herein, we report the identification and subsequent optimization of a series of indole-based fluoroallylamine inhibitors of LOXL2. The result of this medicinal chemistry campaign is (), a potent, irreversible inhibitor that is >300-fold selective for LOXL2 over LOX.

Lipopolysaccharide induces steroid-resistant exacerbations in a mouse model of allergic airway disease collectively through IL-13 and pulmonary macrophage activation.

Background: Acute exacerbations of asthma represent a major burden of disease and are often caused by respiratory infections. Viral infections are recognized as significant triggers of exacerbations; however, less is understood about the how microbial bioproducts such as the endotoxin (lipopolysaccharide (LPS)) trigger episodes. Indeed, increased levels of LPS have been linked to asthma onset, severity and steroid resistance.

Epithelial-mesenchymal transition is driven by transcriptional and post transcriptional modulations in COPD: implications for disease progression and new therapeutics.

COPD is a common and highly destructive disease with huge impacts on people and health services throughout the world. It is mainly caused by cigarette smoking though environmental pollution is also significant. There are no current treatments that affect the overall course of COPD; current drugs focus on symptomatic relief and to some extent reducing exacerbation rates.

Microbiome-focused asthma management strategies.

Asthma is a common, heterogeneous and serious disease with high prevalence globally. Poorly controlled, steroid-resistant asthma is particularly important as there are no effective therapies and it exerts substantial healthcare and societal burden. The role of microbiomes, particularly in chronic diseases has generated considerable interest in recent times.

New therapeutic targets for the prevention of infectious acute exacerbations of COPD: role of epithelial adhesion molecules and inflammatory pathways.

Chronic respiratory diseases are among the leading causes of mortality worldwide, with the major contributor, chronic obstructive pulmonary disease (COPD) accounting for approximately 3 million deaths annually. Frequent acute exacerbations (AEs) of COPD (AECOPD) drive clinical and functional decline in COPD and are associated with accelerated loss of lung function, increased mortality, decreased health-related quality of life and significant economic costs. Infections with a small subgroup of pathogens precipitate the majority of AEs and consequently constitute a significant comorbidity in COPD.

Fibulin-1c regulates transforming growth factor-β activation in pulmonary tissue fibrosis.

Tissue remodeling/fibrosis is a major feature of all fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). It is underpinned by accumulating extracellular matrix (ECM) proteins. Fibulin-1c (Fbln1c) is a matricellular ECM protein associated with lung fibrosis in both humans and mice, and stabilizes collagen formation.

RIPLET, and not TRIM25, is required for endogenous RIG-I-dependent antiviral responses.

The innate immune system is our first line of defense against viral pathogens. Host cell pattern recognition receptors sense viral components and initiate immune signaling cascades that result in the production of an array of cytokines to combat infection. Retinoic acid-inducible gene-I (RIG-I) is a pattern recognition receptor that recognizes viral RNA and, when activated, results in the production of type I and III interferons (IFNs) and the upregulation of IFN-stimulated genes.

Recent Developments in Alpha-Glucosidase Inhibitors for Management of Type-2 Diabetes: An Update.

The incidence of diabetes has increased globally in recent years and figures of diabetic patients were estimated to rise up to 642 million by 2040. The disorder is accompanied with various complications if not managed at the early stages, and interlinked high mortality rate and morbidity with time. Different classes of drugs are available for the management of type 2 diabetes but were having certain limitations of their safety.

Interactions between microbiome and lungs: Paving new paths for microbiome based bio-engineered drug delivery systems in chronic respiratory diseases.

Background: The human body is a home to thousands of microbiotas. It is defined as a community of symbiotic, commensal and pathogenic microorganisms that have existed in all exposed sites of the body, which have co-evolved with diet, lifestyle, genetic factors and immune factors. Human microbiotas have been studied for years on their effects with relation to health and diseases.

Respiratory syncytial virus co-opts host mitochondrial function to favour infectious virus production.

Although respiratory syncytial virus (RSV) is responsible for more human deaths each year than influenza, its pathogenic mechanisms are poorly understood. Here high-resolution quantitative imaging, bioenergetics measurements and mitochondrial membrane potential- and redox-sensitive dyes are used to define RSV's impact on host mitochondria for the first time, delineating RSV-induced microtubule/dynein-dependent mitochondrial perinuclear clustering, and translocation towards the microtubule-organizing centre. These changes are concomitant with impaired mitochondrial respiration, loss of mitochondrial membrane potential and increased production of mitochondrial reactive oxygen species (ROS).

IL-22 and its receptors are increased in human and experimental COPD and contribute to pathogenesis.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of morbidity and death globally. The lack of effective treatments results from an incomplete understanding of the underlying mechanisms driving COPD pathogenesis.Interleukin (IL)-22 has been implicated in airway inflammation and is increased in COPD patients.

Oligonucleotide therapy: An emerging focus area for drug delivery in chronic inflammatory respiratory diseases.

Oligonucleotide-based therapies are advanced novel interventions used in the management of various respiratory diseases such as asthma and Chronic Obstructive Pulmonary Disease (COPD). These agents primarily act by gene silencing or RNA interference. Better methodologies and techniques are the need of the hour that can deliver these agents to tissues and cells in a target specific manner by which their maximum potential can be reached in the management of chronic inflammatory diseases.

Chitinase-like protein YKL-40 correlates with inflammatory phenotypes, anti-asthma responsiveness and future exacerbations.

Background: Asthma is a heterogeneous chronic airway disease, which may be classified into different phenotypes. YKL-40 is a chitin-binding glycoprotein with unclear functions, but its expression is associated with inflammation and tissue remodeling. However, few studies have explored whether YKL-40 is associated with inflammatory phenotypes of asthma.

Polycomb repressive complex 2 is a critical mediator of allergic inflammation.

Strategies that intervene with the development of immune-mediated diseases are urgently needed, as current treatments mostly focus on alleviating symptoms rather than reversing the disease. Targeting enzymes involved in epigenetic modifications to chromatin represents an alternative strategy that has the potential to perturb the function of the lymphocytes that drive the immune response. Here, we report that 2 major epigenetic silencing pathways are increased after T cell activation.

Molecular links between COPD and lung cancer: new targets for drug discovery?

COPD and lung cancer are leading causes of morbidity and mortality worldwide, and they share a common environmental risk factor in cigarette smoke exposure and a genetic predisposition represented by their incidence in only a fraction of smokers. This reflects the ability of cigarette smoke to induce an inflammatory response in the airways of susceptible smokers. Moreover, COPD could be a driving factor in lung cancer, by increasing oxidative stress and the resulting DNA damage and repression of the DNA repair mechanisms, chronic exposure to pro-inflammatory cytokines, repression of innate immunity and increased cellular proliferation.

Group 2 Innate Lymphoid Cells Are Redundant in Experimental Renal Ischemia-Reperfusion Injury.

Acute kidney injury (AKI) can be fatal and is a well-defined risk factor for the development of chronic kidney disease. Group 2 innate lymphoid cells (ILC2s) are innate producers of type-2 cytokines and are critical regulators of homeostasis in peripheral organs. However, our knowledge of their function in the kidney is relatively limited.

Platelet activating factor receptor regulates colitis-induced pulmonary inflammation through the NLRP3 inflammasome.

Extra-intestinal manifestations (EIM) are common in inflammatory bowel disease (IBD). One such EIM is sub-clinical pulmonary inflammation, which occurs in up to 50% of IBD patients. In animal models of colitis, pulmonary inflammation is driven by neutrophilic infiltrations, primarily in response to the systemic bacteraemia and increased bacterial load in the lungs.

Functional effects of the microbiota in chronic respiratory disease.

The composition of the lung microbiome is increasingly well characterised, with changes in microbial diversity or abundance observed in association with several chronic respiratory diseases such as asthma, cystic fibrosis, bronchiectasis, and chronic obstructive pulmonary disease. However, the precise effects of the microbiome on pulmonary health and the functional mechanisms by which it regulates host immunity are only now beginning to be elucidated. Bacteria, viruses, and fungi from both the upper and lower respiratory tract produce structural ligands and metabolites that interact with the host and alter the development and progression of chronic respiratory diseases.

Identification of biomarkers and genetic approaches toward chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease accounts as the leading cause of mortality worldwide prominently affected by genetic and environmental factors. The disease is characterized by persistent coughing, breathlessness airways inflammation followed by a decrease in forced expiratory volume and exacerbations, which affect the quality of life. Determination of genetic, epigenetic, and oxidant biomarkers to evaluate the progression of disease has proved complicated and challenging.